CONCLUSIONS
Complex lymphatic anomalies can be debilitating, and complications of
lymphatic leak can be life-threatening. Unfortunately, the field lacks
basic natural history outcome trials and any prospective interventional
trials dedicated to the treatment of symptomatic lymphatic anomalies or
lymphatic leak. What is certain, however, is the need for a
multidisciplinary, coordinated approach to the management of lymphatic
leak. Management can be triaged based on the rate of lymphatic leak (low
vs high flow) with aggressive nutritional support. Patience is mandatory
as reduction in lymphatic flow can take weeks to achieve. Lymphatic
imaging, surgical, and endolymphatic techniques continue to advance. The
expanding identification of genetic variants that drive abnormal
lymphatic disease has opened the door to new pharmacotherapy options to
augment disease. With such advancements on many fronts coordinated
prospective trials may be on the horizon.
Conflict of Interests: T.A.N. has consulted for Novartis
phamaceuticals to develop consensus guidelines for PIK3CA-related
overgrowth disorders. All additional authors have no financial/personal
conflicts to disclose
REFERENCES
1. Lizaola, B., et al., Review article: the diagnostic approach
and current management of chylous ascites. Aliment Pharmacol Ther,
2017. 46 (9): p. 816-824.
2. Bender, B., V. Murthy, and R.S. Chamberlain, The changing
management of chylothorax in the modern era. Eur J Cardiothorac Surg,
2016. 49 (1): p. 18-24.
3. Bernet-Buettiker, V., et al., Antithrombin activity in children
with chylothorax. Eur J Cardiothorac Surg, 2006. 29 (3): p.
406-9.
4. Vignes, S. and J. Bellanger, Primary intestinal
lymphangiectasia (Waldmann’s disease). Orphanet J Rare Dis, 2008.3 : p. 5.
5. Bellini, C., et al., Congenital fetal and neonatal visceral
chylous effusions: neonatal chylothorax and chylous ascites revisited. A
multicenter retrospective study. Lymphology, 2012. 45 (3): p.
91-102.
6. Bialkowski, A., et al., Congenital chylothorax: a prospective
nationwide epidemiological study in Germany. Arch Dis Child Fetal
Neonatal Ed, 2015. 100 (2): p. F169-72.
7. Pinto, E., et al., Neonatal lymphatic flow disorders: impact of
lymphatic imaging and interventions on outcomes. J Perinatol, 2020.
8. Steinemann, D.C., et al., Atraumatic chylous ascites:
systematic review on symptoms and causes. J Am Coll Surg, 2011.212 (5): p. 899-905 e1-4.
9. Hibbeln, J.F., M.D. Wehmueller, and A.C. Wilbur, Chylous
ascites: CT and ultrasound appearance. Abdom Imaging, 1995.20 (2): p. 138-40.
10. Dori, Y., Novel Lymphatic Imaging Techniques. Tech Vasc
Interv Radiol, 2016. 19 (4): p. 255-261.
11. Notohamiprodjo, M., et al., MR lymphangiography at 3.0 T:
correlation with lymphoscintigraphy. Radiology, 2012. 264 (1):
p. 78-87.
12. Dori, Y., M.M. Zviman, and M. Itkin, Dynamic contrast-enhanced
MR lymphangiography: feasibility study in swine. Radiology, 2014.273 (2): p. 410-6.
13. Krishnamurthy, R., et al., Imaging the central conducting
lymphatics: initial experience with dynamic MR lymphangiography.Radiology, 2015. 274 (3): p. 871-8.
14. Biko, D.M., et al., Intrahepatic dynamic contrast MR
lymphangiography: initial experience with a new technique for the
assessment of liver lymphatics. Eur Radiol, 2019. 29 (10): p.
5190-5196.
15. Dori, Y., et al., Intramesenteric dynamic contrast pediatric
MR lymphangiography: initial experience and comparison with intranodal
and intrahepatic MR lymphangiography. Eur Radiol, 2020.30 (10): p. 5777-5784.
16. Bellini, C., et al., Congenital Chylothorax of the Newborn:
Diagnosis and Treatment in Three Pictures. Lymphology, 2016.49 (3): p. 150-6.
17. Dorsi, M., et al., Prenatal factors associated with neonatal
survival of infants with congenital chylothorax. J Perinatol, 2018.38 (1): p. 31-34.
18. Zabeck, H., et al., Management of chylothorax in adults: when
is surgery indicated? Thorac Cardiovasc Surg, 2011. 59 (4): p.
243-6.
19. Giefer, M.J., K.F. Murray, and R.B. Colletti, Pathophysiology,
diagnosis, and management of pediatric ascites. J Pediatr Gastroenterol
Nutr, 2011. 52 (5): p. 503-13.
20. Bellini, C., et al., Octreotide for congenital and acquired
chylothorax in newborns: A systematic review. J Paediatr Child Health,
2018. 54 (8): p. 840-847.
21. Fishman, S., Truncal, Visceral, and Genital Vascular
Malformations , in Mulliken and Young’s Vascular Anomalies:
Hemangiomas and Malformations , J. Mulliken, P. Burrows, and S. Fishman,
Editors. 2013, Oxford University Press: New York, New York. p. 966-1016.
22. Lopez-Gutierrez, J.C. and J.A. Tovar, Chylothorax and chylous
ascites: management and pitfalls. Semin Pediatr Surg, 2014.23 (5): p. 298-302.
23. Epaud, R., et al., Therapeutic strategies for idiopathic
chylothorax. J Pediatr Surg, 2008. 43 (3): p. 461-5.
24. Camoglio, F.S., et al., Treatment of neonatal chylous ascites
using a modified Denver peritoneovenous shunt: a case report. Pediatr
Med Chir, 2003. 25 (2): p. 145-7.
25. Huang, Y., et al., Management of refractory chylous ascites
with peritoneovenous shunts. J Vasc Surg Venous Lymphat Disord, 2017.5 (4): p. 538-546.
26. Hodges MM, C.T., Meyers M, Kulungowski A, Marwan AI, Nakano T,
Behrendt N, Liechty KL, Massive fetal chylothorax successfuly
treated with postnatal talc pleurodesis: a case report and review of the
literature. Journal of Pediatric Surgery Case Reports, 2016.9 : p. 1-4.
27. Brissaud, O., et al., Congenital idiopathic chylothorax in
neonates: chemical pleurodesis with povidone-iodine (Betadine). Arch
Dis Child Fetal Neonatal Ed, 2003. 88 (6): p. F531-3.
28. Nissen A, T.F., Edwards M, Thoracoscopically-assisted
doxycycline sclerotherapy for a microcystic thoracoabdominal lymphatic
malformation in a 3-month old patient. Journal of Pediatric Surgery
Case Reports, 2016. 5 : p. 12-14.
29. Spagnol, L., et al., Preoperative administration of Sudan III
and successful treatment of persistent chylous ascites in a neonate. J
Pediatr Surg, 2011. 46 (5): p. 994-7.
30. Mitsunaga, T., et al., Successful surgical treatment of two
cases of congenital chylous ascites. J Pediatr Surg, 2001.36 (11): p. 1717-9.
31. Kuroiwa, M., et al., Successful laparoscopic ligation of the
lymphatic trunk for refractory chylous ascites. J Pediatr Surg, 2007.42 (5): p. E15-8.
32. Hayashida, K., S. Yamakawa, and E. Shirakami, Lymphovenous
anastomosis for the treatment of persistent congenital chylothorax in a
low-birth-weight infant: A case report. Medicine (Baltimore), 2019.98 (43): p. e17575.
33. Taghinia, A.H., et al., Lymphaticovenous bypass of the
thoracic duct for the treatment of chylous leak in central conducting
lymphatic anomalies. J Pediatr Surg, 2019. 54 (3): p. 562-568.
34. Srinivasa, R.N., et al., Endolymphatic Interventions for the
Treatment of Chylothorax and Chylous Ascites in Neonates: Technical and
Clinical Success and Complications. Ann Vasc Surg, 2018. 50 :
p. 269-274.
35. Majdalany, B.S., et al., Pediatric lymphangiography, thoracic
duct embolization and thoracic duct disruption: a single-institution
experience in 11 children with chylothorax. Pediatr Radiol, 2018.48 (2): p. 235-240.
36. Biko, D.M., et al., Pediatric pulmonary lymphatic flow
Disorders: Diagnosis and management. Paediatr Respir Rev, 2019.
37. Greenlee, R., et al., Developmental disorders of the lymphatic
system. Lymphology, 1993. 26 (4): p. 156-68.
38. Venot, Q., et al., Targeted therapy in patients with
PIK3CA-related overgrowth syndrome. Nature, 2018. 558 (7711):
p. 540-546.
39. Li, D., et al., ARAF recurrent mutation causes central
conducting lymphatic anomaly treatable with a MEK inhibitor. Nat Med,
2019. 25 (7): p. 1116-1122.
40. Adams, D.M., et al., Efficacy and Safety of Sirolimus in the
Treatment of Complicated Vascular Anomalies. Pediatrics, 2016.137 (2): p. e20153257.
41. Mizuno, T., et al., Model-based precision dosing of sirolimus
in pediatric patients with vascular anomalies. Eur J Pharm Sci, 2017.109S : p. S124-S131.
42. Cho, S., et al., Chylous Manifestations and Management of
Gorham-Stout Syndrome. Korean J Thorac Cardiovasc Surg, 2019.52 (1): p. 44-46.
Figure 1: The lymphatic system is a unidirectional transport
system to return fluid to the blood circulation 1a: Intestinal
lymphatics drain from mesenteric nodes to the cysterna chyli located
around the aortic hiatus of the diaphragm and ascends cephalad through
the thoracic duct to empty into the blood circulation via the subclavian
to brachiocephalic veins. Pulmonary lymphatics drain from paratracheal
and bronchopulmonary lymph nodes to right and left thoracic ducts to
similarly empty into subclavian to brachiocephalic veins. The
illustration depicts select lymphatics of the left lung and small
intestine in a healthy neonate (1) thoracic duct (2) left
brachiocephalic vein and branches (3) inferior vena cava (4) cysterna
chyli. 1b: The illustration depicts select abnormalities of the
lymphatic system (5) idiopathic stenosis of the thoracic duct; results
in impaired lymphatic drainage, increased trans-pleural filtration
pressure (lymphatic hypertension), retrograde lymphatic flow and
increased permeability that results in lymphatic leak (6) large region
of pulmonary lymphangiomatosis (over proliferation of lymphatic vessels)
and lymphangiectasia (inappropriately dilated lymphatic vessels)
enveloping the ventral surface of the lung; results in failure of
appropriate lymphatic drainage (7) chylothorax collecting in the left
pleural cavity (8) chylous ascites collecting in peritoneum causing a
distended abdomen.
Figure 2: 2a) Maximal intensity projection (MIP) coronal
projection of intranodal DCMRL in patient with KLA showing massively
dilated and tortuous thoracic duct (arrow) and bilateral pulmonary
perfusion (arrowheads) as well as mediastinal perfusion. 2b)MIP coronal projection of IN-DCMRL in patient with an EPHB4 mutation and
lymphatic conduction disorder showing dermal backflow (arrowheads) and
no flow into the thorax. 2c) MIP coronal projection of
intrahepatic DCMRL in the same patient showing peritoneal leak (arrow),
retrograde mesenteric flow, and conduction up left sided paravertebral
channels supplying the left sided posterior intercostal networks
(arrowhead).
Figure 3: Management of a lymphatic leak